Kidney diseases such as chronic nephritis usually show complicated and various symptoms, and for such kidney diseases, it is important to apply a suitable treatment thereto as early as possible so that a transition into chronic renal insufficiency, which requires dialysis treatment, can be avoided, or can be delayed as long as possible. In case of the transition from the initial stage of kidney diseases into chronic renal insufficiency, it is said that it is important to find, as check points for determining the prognosis inclemency, a continuous high proteinuria or hypertension from a clinical view point, or recently interstitial fibrosis as well as glomerulo-sclerosis from a histological view point. However, no decisive method has actually been established yet for accurate diagnosis of the prognosis of kidney diseases, and it has been desired to develop a useful method for diagnosis and for examination.
On the other hand, fatty acid binding protein (FABP) is known to be a group of proteins of a molecular weight of about 15 kilodalton, existing in cytosol, and having an ability of binding to a fatty acid. The physiological functions of these proteins are considered to participate in the regulation of metabolic enzyme systems by transfer or accumulation of fatty acid within the cells, but the detailed physiological activities of these proteins have not been clarified yet. There have been known at least seven molecules of FABP such as liver-type (L-FABP), intestine-type (I-FABP), heart muscle-type (H-FABP), brain-type (B-FABP), cutaneous/epidermal-type (C-FABP/E-FABP), fat cell-type (aP2), peripheral neuron-type (myelin-P2), etc., and the primary structures thereof have been determined. All of these FABPs show an ability of binding to a fatty acid, and some of them have a common region wherein a sequence has been duly preserved, so that it is considered that they are a family developed from the common ancestor genes. However, each FABP has a different primary structure, and shows a unique histologic distribution pattern. The nomenclature of FABP means in which organ such FABP is firstly found, but does not mean that such FABP exclusively exists in such organs.
Aiming at FABP, the following diagnostic methods have been known. JP-4-31762-A discloses that the level of H-FABP derived from human heart muscle in serum or urine can be quantitatively assayed by immunoassay using an antibody in order to diagnose myocardial infarction. WO 93/08276 and Kanda et al., Gastroenterology, vol. 110, p. 339-343, 1996 disclose that since the I-FABP level in serum is extremely increased during the small intestine ischemia, etc., I-FABP may be a useful diagnosis marker for intestine diseases. However, they do not have any relation with kidney diseases, and they are concerned with the detection of FABP as an indicator, which leaks accompanied by tissue injury during ischemia, but they never aim at the existence thereof in the tissues.
Recently, YAMAZAKI et al. reported that the existence of L-FABP in large bowel cancer or metastasized lesion thereof is concerned with the malignancy or prognosis of cancer, and the higher the existing amount of L-FABP is, the better the prognosis is (the Gist of the 47th Large Bowel Cancer Seminar, p. 42, 1997). However, this is a finding for a specific tissue such as large bowel cancer.
Moreover, kidney-type FABP existing at male rat kidney has been known to be derived from α2u-globulin, and JP-5-333025-A discloses that the increase in urinary α2u-globulin level can be determined in order to diagnose the α2u-globulin nephropathy which is caused in male rats by the administration of chemical substances. However, it is a mere method for a specific nephropathy model, wherein α2u-globulin remarkably accumulates.
As mentioned above, no method for diagnosis or examination utilizing a relation between FABP in kidney tissues and kidney has been known.